This research will examine in vivo and in vitro the immunology and immunopathology of host defense mechanisms against Chlamydia trachomatis employing an inbred (BALB/c) nude (athymic) (nu/nu) mouse model. The infecting agent will be the mouse pneumonitis agent (MoPn), a strain of C. trachomatis given intranasally. We have shown nu/nu mice to be significantly more susceptible than nu/plus (furred, heterozygous littermates) to pulmonary infection with MoPn, a defect correctable by thymic reconstitution. Nu/plus animals also produce antibody more effectively than nu/nu mice to MoPn. Studies will involve reconstitution of nu/nu mice with normal and immune nu/plus whole spleen cells selectively depleted of T or B cells by the use of specific antibody/complement (cytotoxicity) or passage through nylon wool columns. Attempts will also be made to protect by IV transfer of immune nu/plus serum to both unimmunized nu/nu and nu/plus recipients. The effect of prior intranasal immunization of nu/plus and nu/nu mice on disease course will be observed (to study the T cell dependence of immunization), and evidence for the importance of secretory IgA produced in this manner will be elicited with attempts to detect it in pulmonary lavage fluid by specific immunofluorescent methods. I will also look for pulmonary IgA after intrauterine and intragastric immunization (heterotopic immunization). Immunization will also be used to study the possible relationship between exacerbation at the disease process and an overly exuberant immune response. To this end, quantitative lung cultures for MoPn, histology, and time of death will be correlated to see if prior immunization leads to more severe pulmonary disease in some circumstances. In vitro studies of the ability of specifically and nonspecifically activated macrophages to inhibit MoPn replication (judged by cell lysis and quantitative culturing) will be performed as well as in vitro adherence studies of MoPn to nu/nu and nu/plus tracheal cultures. A genital model of infection in nu/nu mice will also be developed and human strains of C. trachomatis employed in later experiments.